Synergism Between Leukotriene B4 and Thromboxane A2 in Mediating Acid Aspiration Injury

摘要

Acid aspiration leads to thromboxane (Tx) dependent lung neutrophil (PMN) sequestration associated with microvascular permeability increase. Leukotriene (LT) B4 is postulated to be a co-factor in the Tx-induced inflammatory response. This study tests the interaction between LTB4 and TX focusing on LTB4 induction of PMN sequestration following acid aspiration. Anesthetized rats underwent tracheostomy and insertion of a cannula into a left lung segment. This was followed by instillation of either 0.1 ml 0.1N HCl (n=18) or 0.1 ml saline in control rats (n=18). When assayed at three hours acid aspiration led to increased plasma levels of LTB4 and TxB2, higher than control values (p<0.05). The rise in plasma LTB4 was correlated (p<0.05, r=0.83) with sequestration of neutrophils in the non-aspirated lung. There were 95 PMN/10 high power fields (HPF) in the aspirated and 45 PMN/10 HPF in the non-aspirated side, higher than control values of 8 PMN/10 HPF and 5 PMN/10 HPF (both p<0.05). The entrapment of PMN was associated with an increase in protein concentration in bronchoalveolar lavage (BAL) of the aspirated and non-aspirated sides 4520 ug/ml and 2320 ug/ml respectively relative to saline aspirated control rats 480 ug/ml and 410 ug/ml (both p<0.05). There was an increase in lung wet to dry weight ratio (W/d) of 6.5 and 5.3, higher than control values of 3.4 and 3.3 (both p<0.05). Pretreatment of other rats (n=18) with the lipoxygenase inhibitor diethylcarbamazine (DEC) IV 90 mg/kg as a bolus followed by 40 mg/kg/h prevented aspiration induced rise in plasma LTB4 and TxB2. Further, there was an attenuation of: lung leukosequestration (56 and 28 PMN/10 HPF); protein leak in BAL (2120 ug/ml, 1240 ug/ml) and lung edema (5.0,3.6) (all p<0.05).